5EIK

Structure of a Trimeric Intracellular Cation channel from C. elegans in the absence of Ca2+

Summary for 5EIK

• Entry DOI: 10.2210/pdb5eik/pdb
• Related: 5EGI
• Descriptor: Uncharacterized protein Y57A10A.28, [(2R)-1-octadecanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phospho ryl]oxy-propan-2-yl] (8Z)-icosa-5,8,11,14-tetraenoate, 1-PALMITOYL-2-LINOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE, ... (7 entities in total)
• Functional Keywords: membrane protein, cation channel
• Biological source: Caenorhabditis elegans
• Total number of polymer chains: 1
• Total formula weight: 33206.07

Authors

Hu, M.H.,Yang, H.T.,Liu, Z.F. (deposition date: 2015-10-30, release date: 2016-10-05, Last modification date: 2023-11-08)

Primary citation

Yang, H.T.,Hu, M.H.,Guo, J.L.,Ou, X.M.,Cai, T.X.,Liu, Z.F.
Pore architecture of TRIC channels and insights into their gating mechanism.
Nature, 538:537-541, 2016

PubMed Abstract: Intracellular Ca signalling processes are fundamental to muscle contraction, neurotransmitter release, cell growth and apoptosis. Release of Ca from the intracellular stores is supported by a series of ion channels in sarcoplasmic or endoplasmic reticulum (SR/ER). Among them, two isoforms of the trimeric intracellular cation (TRIC) channel family, named TRIC-A and TRIC-B, modulate the release of Ca through the ryanodine receptor or inositol triphosphate receptor, and maintain the homeostasis of ions within SR/ER lumen. Genetic ablations or mutations of TRIC channels are associated with hypertension, heart disease, respiratory defects and brittle bone disease. Despite the pivotal function of TRIC channels in Ca signalling, their pore architectures and gating mechanisms remain unknown. Here we present the structures of TRIC-B1 and TRIC-B2 channels from Caenorhabditis elegans in complex with endogenous phosphatidylinositol-4,5-biphosphate (PtdIns(4,5)P, also known as PIP) lipid molecules. The TRIC-B1/B2 proteins and PIP assemble into a symmetrical homotrimeric complex. Each monomer contains an hourglass-shaped hydrophilic pore contained within a seven-transmembrane-helix domain. Structural and functional analyses unravel the central role of PIP in stabilizing the cytoplasmic gate of the ion permeation pathway and reveal a marked Ca-induced conformational change in a cytoplasmic loop above the gate. A mechanistic model has been proposed to account for the complex gating mechanism of TRIC channels.

PubMed: 27698420
DOI: 10.1038/nature19767

Experimental method

X-RAY DIFFRACTION (2.3 Å)